The overall objectives are: (a) to gain insight into the pathophysiology of acute renal failure (ARF) in man; (b) to develop a convenient, rapid, and reliable means for assessing renal function in the critically ill; (c) to reduce the incidence morbidity and mortality of ARF following cardiac surgery. In a prospective six-month study of 204 heart surgery patients five (2.5%) had documented renal dysfunction (RD) and five (2.5%) developed ARF. Preoperative left ventricular dysfunction and prolonged cardiopulmonary bypass (CPB) were important predictors of subsequent RD/ARF: CPB pressure, per se, was not. Twenty-two patients with non-azotemic postoperative courses demonstrated moderate depression of cardiac function with rapid return to normal if the age-adjusted glomerular filtration rate (98 plus or minus 30 ml/min/1.73m2 within 24-hours of surgery). Detailed pathophysiological, clinical and therapuetic data were reviewed in 17 patients who developed ARF (65% mortality) and 12 who experienced severe RD without ARF (17% mortality). RD and ARF patients demonstrated early postoperative similar pathophysiology with severe depression of cardiac and renal function. Superposition of further hemodynamic or toxic insults upon ischemic kidneys was usually necessary for ARF to occur. The demonstration of a potentially reversible precursor state, RD, in 13 of 17 ARF patients has significant therapeutic implications. Separate studies of the effect of intra-aortic balloon counterpulsation and sodium nitroprusside on renal function in the postoperative period are nearing completion, and a detailed analysis of glomerular and tubular function characteristics in 50 patients with RD or ARF is being undertaken, including studies to define glomerular permselectivity to marcomolecules, and the importance of tubular leakage of glomerular filtrate in ARF. Additional therapeutic protocols are planned.